Humoral and Lung Protease-Antiprotease: Role in COPD. Our major objectives are to define the roles of humoral and lung protease-antiprotease relationshipes and of cigarette smoking (pack-years) as risk factors for chronic obstructive pulmonary disease (COPD). Assay of polymorphonuclear leukocyte (PMN) lysosomal elastase, chmotrypsin-like enzyme and collagenase activity (neutral proteases) and of serum inhibitory capacity for these proteases in healthy persons and in cigarette smokers and nonsmokers with COPD will reveal alteration of humoral protease-antiprotease relationship for each of the neutral proteases that may be associated with COPD and also with smoking. The inhibitory capacity of a person's serum alphal-antitrypsin (AAT) for the combined protease activities in his own PMN lysosomal extract will provide an overall measure of endogenous protease inhibitory capacity. Comparison of the sensitivity of pulmonary alveolar macrophage (obtained by bronchopulmonary lavage) lysosomal elastase, chymotrypsin-like enzyme and collagenase activity to inhibition by AAT with that of the corresponding PMN proteases, may indicate the relative roles of these cells in COPD. Assay of the activity and identification of the subcellular localization of the antiprotease content of PAM will indicate the physiologic role of antiprotease in this cell. Comparison in smoker and nonsmoker bronchopulmonary lavage fluid of (1) active and inactive fractions of AAT, alpha2macroglobulin and bronchial mucus protease inhibitor, (1) active and inactive fractions of the neutral lysosomal proteases, (3) the inhibitory capacit of lavage fluid for these proteases will indicate the effect cigarette smoking may have on lung protease-antiprtease relationships. Analysis of variance models will be applied to test the usefulness of the measured humoral and bronchopulmonary protease-antiprotease relationships and of cigarette smoking history for describing a composite score for pulmonary function tests (pulmonary function index).